Process for the preparation of diphenyl ethers

ABSTRACT

In a process for the preparation of a diphenyl ether substituted in the 4,4&#39;-position and/or the 2,2&#39;-position relative to the ether oxygen atom by reaction of a reactive benzene compound substituted in the 1-position and the 2- or 4-position with a salt of nitrous acid, the improvement in that the reaction is carried out in the presence of a quaternary onium salt in water.

This is a continuation of application Ser. No. 731,474, filed Oct. 12,1976 and now abandoned.

The invention relates to a new process for the preparation of diphenylethers, substituted in the 4,4'-position and/or the 2,2'-position, byreaction of reactive benzene compounds, which are substituted in the1-position and the 4-position or in the 1-position and the 2-position,with salts of nitrous acid.

A process for the preparation of 4,4'-disubstituted diphenyl ethers byreaction of reactive p-substituted halogenobenzene or nitrobenzenecompounds with sodium nitrite is known from DT-OS (German PublishedSpecification) No. 2,037,781. The reaction is carried out in polarorganic solvents (ε<7) at temperatures of 100° to 220° C. The molarratio of the reactive 1,4-disubstituted benzene compound:sodium nitriteis 1:1 to 4.5.

However, the process has the serious disadvantage that small amounts ofnitrophenolates which, in the organic solvents used, tend towardsexplosive decomposition at temperatures above 100° C., are formed asby-products. The process is therefore too unsafe for use on anindustrial scale (see Houben-Weyl, 4th edition, 1963, volume VI/2, page35).

A further process for the preparation of 4,4'-disubstituted diphenylethers is described in DT-AS (German Published Specification) No.1,290,147. According to this process, 1-halogeno-4-nitro-phenylcompounds are condensed, in polar organic solvents in the presence of aconcentrated aqueous alkali metal hydroxide, to form4,4'-dinitro-diphenyl ethers. This reaction has the disadvantage that itcan be used only for the preparation of those diphenyl ethers which donot contain any groups sensitive to alkali, for example which do notcontain a nitrile, carboxylic acid amide, ester or trifluoromethylgroup.

SUMMARY OF THE INVENTION

Broadly, this invention contemplates an improvement in a process for thepreparation of a diphenyl ether substituted in the 4,4'-position and/orthe 2,2'-position relative to the ether oxygen atom, wherein a reactivebenzene compound substituted in the 1-position and the 4- or 2-positionis contacted with a salt of nitrous acid by carrying out the process inthe presence of a quaternary onium salt in water.

It has now been found, surprisingly, that it is possible, by reactingreactive benzene compounds with nitrites, to prepare diphenyl ethers,substituted in the 4,4'-position and/or the 2,2'-position, in a simplemanner and without danger and without undesired by-products being formedwhen the reaction is carried out in non-polar organic solvents but inthe presence of quaternary onium compounds in water. This result issurprising because it was to be expected according to the state of theart that, under the reaction conditions employed, namely heating inaqueous solutions rendered alkaline with sodium carbonate, the reactivebenzene compounds would be saponified to phenols. The process accordingto the invention also has the advantage that the costly working up ofthe organic solvents is dispensed with. With the procedure according tothe invention, the substituted diphenyl ethers are in most casesobtained direct in a crystalline form and can be separated off from theaqueous reaction solution in a simple manner. Furthermore, with the aidof the process according to the invention it is also possible to preparesubstituted diphenyl ethers which are substituted by groups sensitive toalkali.

The diphenyl ethers substituted in the 4,4'-position and/or the2,2'-position, which can be prepared according to the invention, arepreferably diphenyl ethers of the formula ##STR1## in which R denotes aNO₂, CN or R"SO₂ group which is in the ortho-position or para-positionrelative to the ether oxygen atom and

R' denotes hydrogen, fluorine, chlorine, a C₁ -C₄ -alkyl, C₁ -C₄ -alkoxyor C₁ -C₄ -alkylmercapto radical, which is optionally substituted byhalogen, or the N(R")₂ radical,

in which

R" repesents alkyl or aryl which is optionally substituted by halogen.

The reactive benzene compounds substituted in the 1-position and4-position or the 1-position and 2-position, which are to be used asstarting compounds, correspond, in particular, to the formula ##STR2##in which Y denotes a halogen atom or the nitro group,

R denotes a NO₂, CN or R"SO₂ group which is in the ortho-position orpara-position relative to Y and

R' has the meaning indicated under formula I.

Examples of R' and R" which may be mentioned are: as C₁ -C₄ -alkylradicals which are optionally substituted by halogen, above all themethyl and trifluoromethyl radical, as C₁ -C₄ -alkoxy radicals which areoptionally substituted by halogen, above all the methoxy andtrifluoromethoxy radical and, as C₁ -C₄ -alkylmercapto radicals whichare optionally substituted by halogen, the methylmercapto andtrifluoromethylmercapto radical.

For R", possible aryl radicals are, above all, optionally substitutedphenyl radicals, for example phenyl radicals substituted by C₁ -C₄-alkyl or halogen, such as the phenyl, chlorophenyl, 2,4-dichlorophenyl,tolyl and xylyl radical.

The quaternary onium salts to be used according to the invention arequaternary ammonium and phosphonium salts of the formula ##STR3## inwhich Z represents nitrogen or, preferably, phosphorus,

R₁, R₂, R₃ and R₄ independently of one another denote optionallysubstituted alkyl, cycloalkyl, aralkyl or aryl, or two adjacent radicalsamongst R₁, R₂, R₃ and R₄, together with the central atom Z andoptionally further hetero-atoms, form a heterocyclic structure and

X³¹ represents a halide, cyanide or hydroxyl ion.

Examples of R₁, R₂, R₃ and R₄ which may be mentioned are: as alkylradicals, above all C₁ -C₁₈ -alkyl radicals, such as the methyl, ethyl,propyl, butyl, heptyl, hexyl, dodecyl and octadecyl radical; as aralkylradicals, benzyl radicals which are optionally substituted by C₁ -C₄-alkyl radicals or methoxy groups or halogen; as aryl radicals, aboveall phenyl radicals which are substituted by C₁ -C₄ -alkyl or C₁ -C₂-alkoxy groups or by halogen atoms and, as cycloalkyl radicals,cyclopentyl and especially cyclohexyl radicals, which are optionallysubstituted by C₁ -C₄ -alkyl radicals.

Examples which may be mentioned of heterocyclic structures which can beformed by two adjacent radicals amongst R₁, R₂, R₃ and R₄, together withthe central atom Z and optionally further hetero-atoms, such as oxygen,sulphur or nitrogen, are, above all, 5-membered and 6-memberedheterocyclic structures, such as the pyrrolidine, piperidine ormorpholine ring.

The following may be mentioned as examples of representatives of theonium salts to be used according to the invention: tetraethyl-ammoniumchloride, tetrabutyl-ammonium bromide, tetrabutyl-ammonium iodide,triethyl-benzyl-ammonium chloride, methylbutyl-piperidinium iodide,tetraethyl-ammonium bromide, tetrabutyl-ammonium chloride,benzyl-methyl-piperidinium iodide, tetraethyl-ammonium cyanide,benzyltrimethyl-ammonium hydroxide, benzyltrimethyl-ammonium cyanide,triphenylbenzyl-phosphonium bromide, benzyldodecyldimethyl-ammoniumchloride, cyclohexyloctyldimethyl-ammonium chloride andtetrabutyl-phosphonium chloride.

Quaternary onium salts of the formula III in which R₁ and R₂independently of one another represent C₁ -C₄ -alkyl and R₃ representsC₁ -C₄ -alkyl or benzyl and R₄ represents C₁ -C₁₄ -alkyl or phenyl, orR₁ and R₂ together with the nitrogen atom form a 5-membered or6-membered heterocyclic structure, have proved particularly useful.

The amount of quaternary onium salt can vary within wide limits. Ingeneral, 0.1 to 10% by weight, preferably 2 to 5% by weight, based onthe weight of the reactive benzene compound to be reacted, have proveduseful.

In general, the process according to the invention is carried out byheating the reactants, that is to say the reactive benzene compounds ofthe formula II, alkali metal nitrites or alkaline earth metal nitrites,quaternary onium compounds and water, to temperatures of 100°-220° C.,preferably 100°-150° C., if appropriate, whilst stirring, until thereaction has ended.

In order to reach temperatures above 100° C., it is appropriate to carryout the reaction in closed reaction vessels under pressure. Reactiontemperatures of up to 130° C. can also be achieved without the use ofpressure by using supersaturated salt solutions. In most cases, thediphenyl ether formed is obtained in a crystalline form and can befiltered off direct. If necessary, the crude product can be purified byknown methods, for example by recrystallisation.

In order to bind the nitrous gases formed during the reaction, alkalimetal carbonates or alkaline earth metal carbonates are advantageouslyalso added to the reactants.

In order to prepare the reaction mixture, alkali metal nitrites oralkaline earth metal nitrites, alkali metal carbonates or alkaline earthmetal carbonates and quaternary onium compounds are dissolved in waterand the benzene compound to be reacted is added to the solution. Thesequence in which the reactants are mixed with one another is notimportant. In order to achieve reasonable reaction times it is essentialthat the benzene compound is at least partially in the liquid phase.This condition is met when the benzene compound dissolves, at least to alimited extent, for example to the extent of 1%, in the aqueous saltsolution at the reaction temperatures and/or when the melting point ofthe benzene compound is below the reaction temperature, that is to saythe benzene compound is in the molten state.

The amount of water is not critical and can be varied within widelimits. It is possible to choose a small amount of water and to carryout the reaction with solutions, of the inorganic salts, which aresaturated when hot; it is also possible to use dilute aqueous solutions,for example 10% strength solutions, of the inorganic salts. It hasproved to be most advantageous so to choose the amount of water thatboth the inorganic salts which are employed and the salts which areformed during the reaction are dissolved at room temperature.

The benzene compound and the nitrite are generally employed in a ratioof 1 mol of benzene compound:1.5-2.5 equivalents of nitrite. When thisratio is used, the amount of carbonate is advantageously about 1 mol ofcarbonate per mol of phenyl compound.

The quaternary onium compounds used as catalysts can be recovered andre-used. For recovery, the crystalline organic reaction product iswashed with an organic solvent, for example alcohol, and this solutionis concentrated. The residue essentially consists of the quaternaryonium compound and still contains only small amounts of the reactionproduct and/or the starting material. The remaining fraction of thequaternary onium compound can be recovered by extracting the aqueoussalt solution. The onium compound obtained in this way, which has beenfreed from solvents and still contains small amounts of organicmaterial, can be re-used to catalyse the reaction.

The 4,4'-dinitro-diphenyl-ether can be reduced in known manner withhydrogen and raney-nickel as catalyst to the corresponding diamines. Thediamines are starting materials for polyamides which can be obtained forexample in a polymerisation-reaction with pyro mellitic acid dianhydrid(DAS No. 12 02 981 and U.S.S.R. Pat. No. 293 070).

EXAMPLE 1

A reaction mixture consisting of 35 g (0.51 mol) of sodium nitrite, 20 g(0.19 mol) of sodium carbonate, 80 ml of water, 2 g (0.012 mol) oftetraethyl-ammonium chloride and 45 g (0.2 mol) of4-chloro-3-nitro-benzotrifluoride is heated to the reflux temperaturefor 2 hours. After cooling, the precipitate is filtered off and washedwith a little dilute hydrochloric acid and then with a little water. Theproduct, which has been pressed off well, is recrystallised fromalcohol. Yield: 30 g (76% of theory) of2,2'-dinitro-4,4'-di-(trifluoromethyl)-diphenyl ether. (Melting point:106°-107° C.).

EXAMPLE 2

A mixture consisting of 86 g (1.25 mols) of sodium nitrite, 53 g (0.5mol) of sodium carbonate, 300 ml of water, 6 g (0.02 mol) oftetrabutyl-phosphonium chloride and 78.5 g (0.5 mol) of4-chloro-nitrobenzene is heated, in an autoclave, to 140° C. for 5hours, whilst stirring and under the autogenous pressure. After coolingand letting-down the autoclave, the solid product is filtered off fromthe aqueous solution and washed, first with 50 ml of water and then with100 ml of methanol.

The methanol solution is collected separately and concentrated todryness since, in addition to a little reaction product, it contains thecatalyst and the latter can be re-used.

The crystalline reaction product is dried. 60 g (90% of theory) of4,4'-dinitro-diphenyl ether (melting point: 140°-141° C.) are obtained.

EXAMPLE 3

A mixture consisting of 40 g (0.255 mol) of 2-chloronitrobenzene, 35 g(0.51 mol) of sodium nitrite, 18 g (0.17 mol) of sodium carbonate, 140ml of water and 2 g (0.007 mol) of tetrabutyl-phosphonium chloride isheated, in an autoclave, to 140° C. for 5 hours, whilst stirring andunder the autogenous pressure. After cooling, the solid product isfiltered off and washed with concentrated hydrochloric acid until nofurther evolution of gas can be discerned. The residue on the filter isthen stirred with 30 ml of alcohol and the mixture is filtered. Theresidue is recrystallised from alcohol. 13.5 g (40% of theory) of2,2'-dinitrodiphenyl ether (melting point: 112°-114° C.) are obtained.

EXAMPLE 4

A mixture consisting of 60 g (0.87 mol) of sodium nitrite, 53 g (0.5mol) of sodium carbonate, 7 g (0.023 mol) of tetrabutyl-phosphoniumchloride, 200 ml of water and 96 g (0.5 mol) of3,4-dichloro-nitrobenzene is heated, in an autoclave, to 140° C. for 7hours, under the autogenous pressure. After cooling, the precipitate isfiltered off and washed, first with concentrated hydrochloric acid, thenwith a little water and finally with a little alcohol. The product whichremains is recrystallised from alcohol. 40 g (48% of theory) of2,2'-dichloro-4,4'-dinitro-diphenyl ether (melting point: 148°-149° C.)are obtained.

EXAMPLE 5

A mixture consisting of 40 g (0.58 mol) of NaNO₂, 20 g (0.19 mol) ofsodium carbonate, 40 ml of water, 20 ml (0.03 mol) of a 50% strengthsolution of benzyldodecyldimethyl-ammonium chloride and 31 g (0.2 mol)of 2-chloro-6-fluorobenzonitrile is heated to the reflux temperature(110° C.) for 4 hours, whilst stirring. The (upper) organic phase isthen separated off and cooled. The solid mass which is obtained is thenrecrystallised from isopropanol. 23.6 g (82% of theory) of3,3'-dichloro-2,2'-dicyano-diphenyl ether (melting point: 194°-195° C.)are obtained.

2-Chloro-6-fluoro-benzonitrile, which was used as the starting compound,was obtained as follows:

A solution of 120 g (2 mols) of potassium fluoride in 100 ml of waterwas treated first with 30 ml of a 50% strength aqueous solution ofbenzyldodecyl-ammonium chloride and then with a solution of 186 g (1mol) of 2-nitro-6-chloro-benzonitrile in 250 ml of toluene. The reactionmixture was heated to 105° C. for 8 hours. After cooling, the organicphase was separated off and the aqueous phase was extracted withchloroform. The organic phase and the chloroform extracts were combinedand washed and then freed from the organic solvent by distillation. Ondistillation of the residue, 35 g of 2-chloro-6-fluoro-benzonitrile(boiling point: 105°-108° C./15 mm Hg) were obtained.

EXAMPLE 6

A mixture of 69 g (1.0 mol) of sodium nitrite, 53 g (0.5 mol) of sodiumcarbonate, 5 g (0.01 mol) of hexadecyltributyl-phosphonium bromide, 220ml of water and 78.5 g (0.5 mol) of 4-chloro-nitrobenzene is heated to140° C. for 7 hours. After cooling, the solid product is filtered offand washed, first with a little dilute hydrochloric acid and then with alittle alcohol. After drying, 61 g (91.5% of theory) of4,4'-dinitrodiphenyl ether (melting point: 139°-140° C.) are obtained.

EXAMPLE 7

A mixture consisting of 8 g (0.115 mol) of sodium nitrite, 5 g (0.05mol) of sodium carbonate, 1 g (0.0029 mol) ofcyclohexyloctyldimethyl-ammonium chloride, 13 ml of water and 12 g(0.049 mol) of 4-chlorophenyl-trifluoromethylsulphone is heated to thereflux temperature for 3 hours. After cooling, the reaction mixture isextracted with 50 ml of methylene chloride. The organic phase isseparated off, dried over sodium sulphate and freed from the solvent bydistillation. The residue is recrystallised from n-hexane 8 g (75% oftheory) of 4,4'-di-(trifluoromethylsulphonyl)-diphenyl ether (meltingpoint: 102°-104° C.) are obtained.

What is claimed is:
 1. In a process for the preparation of a diphenylether substituted in the 4,4'-position and/or the 2,2'-position relativeto the ether oxygen atom by reaction of a reactive benzene compoundsubstituted in the 1- and in the 2- or 4-position, said reactive benzenecompound having the formula ##STR4## in which Y denotes a halogen atomor the nitro group, R denotes an NO₂, CN or R"SO₂ group which is in theortho-position or para-position relative to Y, and R' denotes hydrogenfluorine, chlorine, a C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy or C₁ -C₄-alkylmercapto radical, which is optionally substituted by halogen, orthe N(R")₂ radical in which R" represents alkyl or aryl which isoptionally substituted by halogen, with an alkali or alkaline earthmetal nitrite at 100°-220° C., the improvement which comprises carryingout the reaction in the presence of a quaternary onium salt in water,said quaternary onium salt having the formula ##STR5## in which Zrepresents nitrogen or phosphorous, R₁, R₂, R₃ and R₄ represent C₁₋₁₈alkyl radicals, aralkyl radicals in which the aryl portion is a benzylradical which is optionally substituted by C₁₋₄ alkyl radicals, amethoxy group or halogen, a phenyl radical which is optionallysubstituted by C₁ -C₄ alkyl, C₁ -C₂ alkoxy or by halogen or a cycloalkylradical selected from the group consisting of cyclopentyl and cyclohexylwhich cycloalkyl radical can be optionally substituted by a C₁ -C₄ alkylradical, or two adjacent radicals amongst R₁, R₂, R₃ and R₄ togetherwith the central atom Z and optionally further hetero-atoms, form aheterocyclic structure containing oxygen, sulfur or nitrogen in thering, said heterocyclic structure being a 5- or 6-membered ring and X⁻represents a halide, cyanide or hydroxy ion.
 2. A process according toclaim 1, wherein:A. The quaternary onium salt is selected from the groupconsisting of tetraethyl-ammonium chloride, tetrabutyl-ammonium bromide,tetrabutyl-ammonium iodide, triethyl-benzyl-ammonium chloride,methylbutyl-piperidinium iodide, tetraethyl-ammonium bromide,tetrabutyl-ammonium chloride, benzyl-methylpiperidinium iodide,tetraethyl-ammonium cyanide, benzyltrimethyl-ammonium hydroxide,benzyltrimethyl-ammonium cyanide, triphenylbenzyl-phosphonium bromide,benzyldodecyldimethyl-ammonium chloride,cyclohexyloctyldimethyl-ammonium chloride and tetrabutyl-phosphoniumchloride; B. The quaternary onium salt is present in the reactionmixture in an amount of 0.1 to 10% by weight; and C. The process isconducted at a temperature of 100°-150° C.
 3. A process according toclaim 2, wherein the process is carried out in an autoclave.